The present invention relates to molecular resonance of molecules, in particular molecular resonance generated by laser radiation.
The concept of introducing high Q molecules that may be stimulated by laser light to deliver toxic or therapeutic effects is known from Dunlavy U.S. Pat. No. 5,313,315. However, the direct stimulation of natural biological processes by means of molecular resonance using modulated or selective wavelength lasers has hitherto proved to be impossible. This is because of the scattering nature of the medium, the close proximity of many resonances in natural molecules and the difficulty of differentially raising the temperature and thereby the reactivity of individual desired molecules.
The present invention defines an apparatus and method which overcomes some of these problems and covers the nature and type of molecule susceptible to differential stimulation.
Many critical chemical reactions in the body are functions of the Cell Surface Cell Adhesion Molecules that are in turn morderated by various integrins. The geometric structure of many Cell Adhesion Molecules and particular integrins is such that they are capable of supporting a resonance at relatively low frequency and surprisingly high Q. Unlike most protein structures which are heavily damped or inherently rigid in structure these molecules generally take the form of a pair of relatively rigid structures separated by space often bridged by a single strand. This structure is especially sensitive to periodic stimulation by a laser source especially when the molecule surface is neutral or slightly negatively charged. The polar and hydrophobic regions of the molecule also differentially absorb energy from laser light. This causes brief alterations in both the structural bond energy and consequently tends to amplify the vibration of the molecule. The effect of this is to slightly increase the chemical reactivity of particular molecules on a cell surface relative to the surrounding molecules of a more generally damped structure or other high Q molecules of a different resonant frequency.
In vivo the scattering of light at suitable excitation wavelengths is extreme and as a result even quite low frequency modulation signals tend to be corrupted by the multiple scatter path lengths and by the delay in absorption and release of photons in those atoms at low energy states.
Also if continuous laser radiation is delivered to a mass of cells the high damping factor of the structure means that in general the overall temperature of the cell mass rises. This occurs even if modulated at the resonant frequency of a particular molecule. The use of laser radiation in this way produces an increase in the reactivity of the entire cell surface which means that no actual change in the reaction products occur because the cells are in general, at equilibrium.
Conversely if very low energy is delivered at the resonance frequency of the cell adhesion molecules or if energy can be delivered as an intermittent pulse of extremely short duration, the cell adhesion molecules and the integrins with their inherently high Q structure tend to maintain a slightly higher temperature than the surrounding molecules. Thus the cell adhesion molecules can be stimulated to a greater reactivity than the surrounding surface molecules.
Many biological processes can be disturbed into a cascade of increasing reactivity if an initial response is initiated. The immune response is a powerful example of this but the nature of biological reactions on the cell surface means that similar cascade reactions occur for a wide variety of initial conditions disturbed from equilibrium. Thus a very small change in the reactivity of a surface molecule for a short time can result in a dramatic change in the chemistry of the cell surface for a considerable period after the stimulation.
This effect depends on the cell chemistry being substantially in equilibrium at the commencement of the delivery of the radiation, otherwise the resonance effect will tend to be swamped by the current dominant reaction. Thus the target cells must be in a relatively neutral pH environment and obviously not engaged in a vigorous metabolic process. Ideally also the cell surface molecule would be neutral or slightly negative as this increases the absorption of photons and so increases the transfer of energy from the laser to the molecule.
Although this limits the use of this method, it has one beneficial effect with respect to therapeutic use in carcinomas. The undifferentiated cells of a carcinoma are generally at equilibrium on the surface as most of the chemical energy of the cell is expended internally in the cell duplication process. This means that the undifferentiated cells of a carcinoma are particularly susceptible to the effect of the method on the surface chemistry since by their nature they conform to the ideal requirements for low energy disturbance of the equilibrium.
It is a critical requirement of this effect that the initial stimulation is periodic and of very low overall energy, as higher energy stimulation would merely raise the temperature of the entire cell by conduction and would not change the reaction equilibrium. To achieve such a change, individual molecules on the cell surface must be at different temperatures. Ideally it would consist of small, directed bursts of light modulated at the frequency of the desired molecule. Unfortunately it is clearly imposbible to direct such a beam in the highly scattering medium of a living human body.
If a conventional laser or simple light beam is directed at a highly-scattering medium, the modulation is eliminated at any substantial frequency because the light paths to any given point are so numerous and of such differing lengths that any modulation is reduced to noise after a few millimetres of the scattering medium. Even at lower frequencies the general level of overall energy delivered to the cells means that conduction and convection tend to raise the overall temperature of the cell surface rather than allow isolated temperature differences to exist for any useful length of time. Further it is impractical to generate a light pulse which is of sufficiently short duration and with a sufficiently high pulse repetition frequency to be of practical use in the stimulation of any resonance of a Q likely to occur in a living cell surface molecule.
This invention provides a means of differentially stimulating at least those molecules susceptible by their structure to resonant stimulus.
The invention and preferred features thereof are defined in the appended claims.